Cancers are diseases of uncontrolled proliferation of abnormal cells. Urothelial carcinoma of the urinary bladder represents more than 90% of all bladder cancers, about 80% of which are non-muscle invasive bladder cancer (NMIBC), a form of superficial cancer. Transurethral resection and radical cystectomy remain the mainstay of treatment for NMIBC and MIBC (muscle invasive bladder cancer), respectively. Intravesical therapy with mitomycin is a preferred adjuvant therapy to surgery aiming at reducing disease recurrence and progression. However, some cancers remain refractory to current biological and chemotherapeutic treatments.
Certain combinations of immunomodulating compositions have been proposed to simultaneously activate innate and adaptive immunity to target tumors. However, toxicity from systemic administration of certain treatments (e.g. CTLA-4 antagonist antibodies) has limited their systemic applications for such treatments. Moreover, despite some early promise, at least one report has indicated that the benefit of such combinations may be limited (see for example International Patent Publication WO2016/23960).
Some immune response modulators have a relatively short half-life in terms of residence time at a given body cavity. It is known that such modulators appear to be cleared or metabolized, or simply diffuse away from a body cavity. This short residence duration may reduce the immune checkpoint modulator's ability to activate some immune system cells at the desired site.
There is thus a substantial ongoing need for new means of controlling the delivery and the activity of immune checkpoint modulators in order to expand their uses and therapeutic benefits.